PROJECT SUMMARY While newborn screening (NBS) programs have saved the lives of thousands of children with inherited disorders, the future success of this vital public health program depends on the ability to accurately assess and balance the benefits and harms of screening. The ongoing development of new testing technologies increases the number of disorders screened, which generates more false positive NBS results. Despite decades of research, the scope and magnitude of harms from false positive NBS results remain poorly understood. Failure to resolve this poor understanding has significant policy, ethical, and research implications. From a policy perspective, it undermines the requisite evaluation of benefits and harms that accompanies decisions about whether to add a disorder to a state NBS panel. From an ethical perspective, it places children and their families at risk for adverse outcomes from a mandatory public health program. From a research perspective, it interferes with the design of effective interventions to mitigate these harms. Therefore, the objective of this study is to comprehensively examine the scope, magnitude, and risk factors for harms to both children who receive false positive NBS results and their families. This study objective will be accomplished through a prospective multistate cohort study of children undergoing NBS and their parents with the following specific aims: (1) To determine the scope and magnitude of harms due to false positive NBS results; (2) To identify parental and child factors associated with harms due to false positive NBS results; and (3) To develop a primary care provider (PCP)?parent communication aid to improve PCP communication with parents of children who receive false positive NBS results. The proposed project will provide the most comprehensive data to-date on post-screening harms for children with false positive NBS results. These data are critical to the success of future efforts to improve and expand NBS in the US.